Posters— Medical Oncology

PRELIMINARY RESULTS OF A PHASE 2 TRIAL OF ORAL PIRITREXIM IN PATMIENTS WITH MALIGNANT FIBROUS HISTIOCYTOMA (MFH)

Patel SR, Jenkins J, Hays C, Beech J, Burgess MA, Papadopoulos NE, Plager C, Pisters PWT, Feig BW, Hunt K, Pollock RE, Benjamin RS. The Sarcoma Center, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas (77030)

Piritrexim is a Epid-soluble antifol with a very high affinity for dihydrofolate reductase. It enters the cell by passive diffusion and has been shown to inhibit growth of methotrexate-resistant cells in vitro. A phase 1 trial of the intravenous preparation revealed a response in a patient with MFH. We studied the oral preparation in patients with metastatic MFH who had received one prior chemotherapy regimen. Patients were required to have histologic confirmation, measurable/evaluable disease, ECOG PS £ 2 and reasonable organ fimetion. Piritrexim. was administered at a starting dose of 25 Ing po TID x 5 consecutive days each week for 3 weeks followed by one week rest off treatment. A total of 10 patients have been treated at our center and are evaluable for response and toxicity. The median age is 55 years (range, 2977 years). There were 5 males and 5 females, all with a ECOG PS of 1. All patients had one prior chemotherapy regimen, 5 patients had prior radiation and 10 patients had prior surgery. Two patients have shown a radiographic response. One patient with a primary tumor in the right thigh (and lung metastases) had a 53% reduction in the measurement of the primary tumor thus qualifying for a partial response. Another patient with metastatic disease in the lungs had a 26% reduction in the size of the lung nodule after 5 months of treatment. Unfortunately, his treatment had to be discontinued since the sponsor terminated their plans for further development of the drug. Follow-up CT scan of the chest on this patient 6 weeks off treatment prior to planned surgery reveals a near complete response with only one tiny residual abnormality. A total of 26 cycles are evaluable for toxicity. One patient each in one cycle each experienced grade 3 nausea, vomiting and fatigue. Overall the treatment was well tolerated. In conclusion, oral piritrexim does seem to have some biologic activity in patients with MFH. Unfortunately, our trial has been terminated as per the sponsor’s request and therefore no more data will be available to truly assess the activity of this drug.